Unfolded Protein Response and A Possible Treatment for CFS
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mariovitali
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OK, Good Luck!
mariovitali
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@skwag
Your post got me interested more regarding Rituximab. So It works by destroying B-Cells. For this reason i entered B-Cells to the topics that i have on my software. Needless to say that i am amazed on how many Topics that i keep match with "B-Cells"
I will re-run the Association Analysis and report back
Your post got me interested more regarding Rituximab. So It works by destroying B-Cells. For this reason i entered B-Cells to the topics that i have on my software. Needless to say that i am amazed on how many Topics that i keep match with "B-Cells"
I will re-run the Association Analysis and report back
Thank you, but I don't think there's a lot you can do for me at this stage. The suggestion to try TUDCA was helpful enough. Your supplement table is interesting as well, but I'm already well acquainted with all those supplements and tried a lot of variations so the specifics of combinations (stages) it suggests have potential to help but do not add enough information for myself to use yet. My existing regimen covers much of it.
Yes I have CFS/whatever, accutane changes and fluoroquinolone toxicity, to name a few. Poor liver enzyme SNPs was the overall picture given by promethease. But even that was no longer useful information by then. ATF6 even if meaningful would only add a little to that. I already found out the most important part of the big picture the hardest way possible [other parts I've ruled out experimentally or already cover preventatively by regimen]. Individual SNPs I have enough reasons not to rely on [to select treatment].
I experience this indirectly. I need choline precursors to maintain mental function but they noticeably affect blood flow negatively and constriction in the day. It's a real hindrance.
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mariovitali
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@Tunguska
My suggestion : Try anything you can to thoroughly check and support your Liver. Anytime you want PM me.
@skwag
As discussed, i am trying to understand the connection between B-Cells and the fact that they matched a lot of the PubMed topics i have under consideration :
Recall that the tool searches in different "perspectives" ( ie being either General or Specific )
The runs for B-Cells :
We see that Rituximab is there but also Immunoglobulins such as IgM and IgE.
Next run :
So there appears to be a connection between B-Cells, Heat-shock Proteins (discussed in this Thread), N-Linked Glycosylation (discussed in this Thread, First post).
So how come N-Linkedglycosylation was found to be associated with Rituximab? From the Wikipedia for N-Linked Glycosylation
Link : https://en.wikipedia.org/wiki/N-linked_glycosylation
Now a run about Rituximab itself :
Notice that a lot of (*itis) but also uti (=urinary tract infection) exist around. Apart from this we see something called ERAD :
I then search for a connection between HSPs, B-Cells and Endoplasmic Reticulum :
Remember that Rituximab works by destroying B-Cells.
At another run, the tool has found a possible association association between TLR and B-Cells
(Note 'tlr' in the results)
[
More about the connection between B-Cells and the ER :
Reference : Signaling Pathways in Liver Disease (2010)
My suggestion : Try anything you can to thoroughly check and support your Liver. Anytime you want PM me.
@skwag
As discussed, i am trying to understand the connection between B-Cells and the fact that they matched a lot of the PubMed topics i have under consideration :
Recall that the tool searches in different "perspectives" ( ie being either General or Specific )
The runs for B-Cells :
We see that Rituximab is there but also Immunoglobulins such as IgM and IgE.
Next run :
So there appears to be a connection between B-Cells, Heat-shock Proteins (discussed in this Thread), N-Linked Glycosylation (discussed in this Thread, First post).
So how come N-Linkedglycosylation was found to be associated with Rituximab? From the Wikipedia for N-Linked Glycosylation
Link : https://en.wikipedia.org/wiki/N-linked_glycosylation
Now a run about Rituximab itself :
Notice that a lot of (*itis) but also uti (=urinary tract infection) exist around. Apart from this we see something called ERAD :
I then search for a connection between HSPs, B-Cells and Endoplasmic Reticulum :
Remember that Rituximab works by destroying B-Cells.
At another run, the tool has found a possible association association between TLR and B-Cells
(Note 'tlr' in the results)
[
More about the connection between B-Cells and the ER :
Reference : Signaling Pathways in Liver Disease (2010)
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Hi Mario,
One reason for all the matches you initially found may be that your topics naturally have a lot overlap with "primary biliary cirrhosis (PBC)," as we've seen in older posts. As PBC is a known autoimmune condition, there has been some studies using Rituximab to treat it. For example, here.
Unfortunately, as of now I can't claim to understand the other links you may have uncovered.
One reason for all the matches you initially found may be that your topics naturally have a lot overlap with "primary biliary cirrhosis (PBC)," as we've seen in older posts. As PBC is a known autoimmune condition, there has been some studies using Rituximab to treat it. For example, here.
Unfortunately, as of now I can't claim to understand the other links you may have uncovered.
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mariovitali
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@skwag
Yes i have seen that regarding PBC as well in other runs.
I did not make any comments for a reason. I just wished to identify that B-Cells, N-Linked Glycosylation and Endoplasmic Reticulum appear to be connected. I do not have the proper knowledge to understand more or to make any further connections on the subjects i posted.
Yes i have seen that regarding PBC as well in other runs.
I did not make any comments for a reason. I just wished to identify that B-Cells, N-Linked Glycosylation and Endoplasmic Reticulum appear to be connected. I do not have the proper knowledge to understand more or to make any further connections on the subjects i posted.
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Violeta
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http://www.ncbi.nlm.nih.gov/pubmed/7729416
Epstein-Barr virus efficiently immortalizes human B cells without neutralizing the function of p53
http://www.ncbi.nlm.nih.gov/pubmed/15890964
Heat shock protein 90 expression in Epstein-Barr virus-infected B cells promotes gammadelta T-cell proliferation in vitro.
Epstein-Barr virus efficiently immortalizes human B cells without neutralizing the function of p53
http://www.ncbi.nlm.nih.gov/pubmed/15890964
Heat shock protein 90 expression in Epstein-Barr virus-infected B cells promotes gammadelta T-cell proliferation in vitro.
mariovitali
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So , here is why i ended up with problems (i think)
5α-Reductase type 1 deficiency or inhibition predisposes to insulin resistance, hepatic steatosis, and liver fibrosis in rodents.
Livingstone DE1, Barat P2, Di Rollo EM2, Rees GA2, Weldin BA2, Rog-Zielinska EA2, MacFarlane DP2, Walker BR2, Andrew R2.
Author information
Abstract
5α-Reductase type 1 (5αR1) catalyses A-ring reduction of androgens and glucocorticoids in liver, potentially influencing hepatic manifestations of the metabolic syndrome. Male mice, homozygous for a disrupted 5αR1 allele (5αR1 knockout [KO] mice), were studied after metabolic (high-fat diet) and fibrotic (carbon tetrachloride [CCl4]) challenge. The effect of the 5α-reductase inhibitor finasteride on metabolism was investigated in male obese Zucker rats. While eating a high-fat diet, male 5αR1-KO mice demonstrated greater mean weight gain (21.6 ± 1.4 vs 16.2 ± 2.4 g), hyperinsulinemia (insulin area under the curve during glucose tolerance test 609 ± 103 vs. 313 ± 66 ng ⋅ mL(-1) ⋅ min), and hepatic steatosis (liver triglycerides 136.1 ± 17.0 vs. 89.3 ± 12.1 μmol ⋅ g(-1)). mRNA transcript profiles in liver were consistent with decreased fatty acid β-oxidation and increased triglyceride storage. 5αR1-KO male mice were more susceptible to fibrosis after CCl4 administration (37% increase in collagen staining). The nonselective 5α-reductase inhibitor finasteride induced hyperinsulinemia and hepatic steatosis (10.6 ± 1.2 vs. 7.0 ± 1.0 μmol ⋅ g(-1)) in obese male Zucker rats, both intact and castrated. 5αR1 deficiency induces insulin resistance and hepatic steatosis, consistent with the intrahepatic accumulation of glucocorticoids, and predisposes to hepatic fibrosis. Hepatic steatosis is independent of androgens in rats. Variations in 5αR1 activity in obesity and with nonselective 5α-reductase inhibition in men with prostate disease may have important consequences for the onset and progression of metabolic liver disease.
5α-Reductase type 1 deficiency or inhibition predisposes to insulin resistance, hepatic steatosis, and liver fibrosis in rodents.
Livingstone DE1, Barat P2, Di Rollo EM2, Rees GA2, Weldin BA2, Rog-Zielinska EA2, MacFarlane DP2, Walker BR2, Andrew R2.
Author information
Abstract
5α-Reductase type 1 (5αR1) catalyses A-ring reduction of androgens and glucocorticoids in liver, potentially influencing hepatic manifestations of the metabolic syndrome. Male mice, homozygous for a disrupted 5αR1 allele (5αR1 knockout [KO] mice), were studied after metabolic (high-fat diet) and fibrotic (carbon tetrachloride [CCl4]) challenge. The effect of the 5α-reductase inhibitor finasteride on metabolism was investigated in male obese Zucker rats. While eating a high-fat diet, male 5αR1-KO mice demonstrated greater mean weight gain (21.6 ± 1.4 vs 16.2 ± 2.4 g), hyperinsulinemia (insulin area under the curve during glucose tolerance test 609 ± 103 vs. 313 ± 66 ng ⋅ mL(-1) ⋅ min), and hepatic steatosis (liver triglycerides 136.1 ± 17.0 vs. 89.3 ± 12.1 μmol ⋅ g(-1)). mRNA transcript profiles in liver were consistent with decreased fatty acid β-oxidation and increased triglyceride storage. 5αR1-KO male mice were more susceptible to fibrosis after CCl4 administration (37% increase in collagen staining). The nonselective 5α-reductase inhibitor finasteride induced hyperinsulinemia and hepatic steatosis (10.6 ± 1.2 vs. 7.0 ± 1.0 μmol ⋅ g(-1)) in obese male Zucker rats, both intact and castrated. 5αR1 deficiency induces insulin resistance and hepatic steatosis, consistent with the intrahepatic accumulation of glucocorticoids, and predisposes to hepatic fibrosis. Hepatic steatosis is independent of androgens in rats. Variations in 5αR1 activity in obesity and with nonselective 5α-reductase inhibition in men with prostate disease may have important consequences for the onset and progression of metabolic liver disease.
Violeta
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Does that give you any extra clues about what might help? Maybe berberine?
Violeta
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Maybe looking at AMPK will provide some insight?
http://selfhacked.com/2014/11/21/natural-ampk-activators/
http://selfhacked.com/2014/11/21/natural-ampk-activators/
mariovitali
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@Violeta
I do not see how the things you are discussing are connected with 5-Alpha Reductase unfortunately
I do not see how the things you are discussing are connected with 5-Alpha Reductase unfortunately
ahmo
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@mariovitali I was just w/ my GP, talked about UDCA, but left w/o an rx, not because of him, but due to my ambivalence. My impression is that it hasn't proved to be a huge benefit, I can only recall now someone saying they'd tried and then quit it. Do you still think it's very important?
Also, I looked at inosine. It's described as antioxidant, anti-peroxynitrite. Any opinions about it?
And 3rd query, re B12. I'm not sure this is the right place, will be creating a new thread. I've reached a stable, very tolerable state, with almost no symptoms or pain. I've been considering injecting B12, which is very expensive. But I'm unclear whether this alone can transform my life, from doing very little activity to being able to tolerate more, better cognition. And I'm unclear whether this would mean I then must increase folate, which has stressed my adrenals in the past. thx.
Also, I looked at inosine. It's described as antioxidant, anti-peroxynitrite. Any opinions about it?
And 3rd query, re B12. I'm not sure this is the right place, will be creating a new thread. I've reached a stable, very tolerable state, with almost no symptoms or pain. I've been considering injecting B12, which is very expensive. But I'm unclear whether this alone can transform my life, from doing very little activity to being able to tolerate more, better cognition. And I'm unclear whether this would mean I then must increase folate, which has stressed my adrenals in the past. thx.
Violeta
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With respect to berberine, "While berberine extract can help to normalize 5-alpha reductase, it also appears to have a major effect on your weight, cholesterol, blood pressure, insulin resistance, and hormones, according to a study from Shanxi Medical University in China."
Violeta
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With respect to AMPK:
Impaired glucose tolerance and insulin resistance are associated with increased adipose 11beta-hydroxysteroid dehydrogenase type 1 expression and elevated hepatic 5alpha-reductase activity.
In addition to glucose transport, lipid and protein synthesis, and fuel metabolism, AMPK regulates a wide array of other physiological events, including cellular growth and proliferation, mitochondrial function and biogenesis, and factors that have been linked to insulin resistance (IR), including inflammation, oxidative and ER stress, and autophagy
mariovitali
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@ahmo
Can you send over the PDF with the Risk Alleles that you have? Could you also send over your Nutrahacker report regarding your P450 CYPs?
Regarding UDCA : TUDCA is a much better option as it is found to be much more "ER Ameliorating" from UDCA Alone. TUDCA on its own may not be doing many things in case you have several other "Redox holes" (my theory).
Again as i have said here previously i am willing to work with you under a Doctor's supervision of course and then you can post your experience if you did/didn't see any difference.
Regarding inosine : I will put it in my software and i will let you know. Regarding B12 i am probably not the right person as i do not know many things about it.
@Violeta
Thank you for all the info you provided They seem to be very interesting indeed.
Can you send over the PDF with the Risk Alleles that you have? Could you also send over your Nutrahacker report regarding your P450 CYPs?
Regarding UDCA : TUDCA is a much better option as it is found to be much more "ER Ameliorating" from UDCA Alone. TUDCA on its own may not be doing many things in case you have several other "Redox holes" (my theory).
Again as i have said here previously i am willing to work with you under a Doctor's supervision of course and then you can post your experience if you did/didn't see any difference.
Regarding inosine : I will put it in my software and i will let you know. Regarding B12 i am probably not the right person as i do not know many things about it.
@Violeta
Thank you for all the info you provided They seem to be very interesting indeed.
ahmo
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I don't have a Nutrahacker report. Risk alleles: genetic genie results?
mariovitali
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Ah Yes, Genetic genie's "Detox profile" lists several P450 CYPs so this will do. Apart from this, please send also the results regarding your RIsk Alleles shown on the PDF (NQO1, GCH1,PDILT,ATF6, etc)
mariovitali
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Dear All,
I am attaching a file which is the basis for the Analysis that i am performing. It may prove useful in case that you are researching any subject possibly relevant to CFS. To generate this file it takes around 11 hours and the it consists of a total of 169790 lines.
FYI @ahmo : The latest addition is "inosine". As an example, if you are interested in "inosine", you search for that entry and then see which Topics are more commonly found along with inosine. In this case we have :
xanthine_oxidase.csv : 1.32 %
uric_acid.csv : 1.18 %
nad.csv : 0.88 %
monosodium_glutamate.csv : 0.78 %
ppp.csv : 0.63 %
benfotiamine.csv : 0.60 %
tmao.csv : 0.49 %
where ppp = Pentose Phosphate Pathway, tmao = Trimethylamine N-Oxide
So we see that "inosine" appears to be associated with Xanthine Oxidase. We search for inosine and xanthine oxidase in Google or Pubmed and we end up with this :
http://www.ncbi.nlm.nih.gov/pubmed/23091148
I am attaching a file which is the basis for the Analysis that i am performing. It may prove useful in case that you are researching any subject possibly relevant to CFS. To generate this file it takes around 11 hours and the it consists of a total of 169790 lines.
FYI @ahmo : The latest addition is "inosine". As an example, if you are interested in "inosine", you search for that entry and then see which Topics are more commonly found along with inosine. In this case we have :
xanthine_oxidase.csv : 1.32 %
uric_acid.csv : 1.18 %
nad.csv : 0.88 %
monosodium_glutamate.csv : 0.78 %
ppp.csv : 0.63 %
benfotiamine.csv : 0.60 %
tmao.csv : 0.49 %
where ppp = Pentose Phosphate Pathway, tmao = Trimethylamine N-Oxide
So we see that "inosine" appears to be associated with Xanthine Oxidase. We search for inosine and xanthine oxidase in Google or Pubmed and we end up with this :
http://www.ncbi.nlm.nih.gov/pubmed/23091148
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Violeta
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I read yesterday that berberine works through Phase II glucuronidation, I should have bookmarked the link.
I just looked up glucuronidation and found this, if it's of interest to anyone.
Glucuronidation, more correctly glucuronosylation, is the addition of glucuronic acid to a substrate. Glucuronidation is often involved in xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids,glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds.[1
I just looked up glucuronidation and found this, if it's of interest to anyone.
Glucuronidation, more correctly glucuronosylation, is the addition of glucuronic acid to a substrate. Glucuronidation is often involved in xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids,glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds.[1